To the uninitiated, the synthesis of peptides may seem to be relatively straightforward. A free carboxyl group in an amino acid, conventionally one having its other reactive group or groups, such as the amino functionality, protected with a removable reaction-blocking group, is coupled to a free amino group in another amino acid whose other reactive groups, including its carboxyl group, are also protected with different reaction-blocking groups. After removing a protecting group from a carboxyl or an amino group in the thus-coupled amino acids, one can then seek to couple an additional amino acid having a protected carboxyl and an unprotected amino group, or vice versa, to the starting amino acid pair, and in theory this can be repeated as often as necessary to increase the length of the peptide chain and give the desired peptide.
The amino acids used are known, as are typical protecting group-providing reagents, coupling agents, activating agents and other materials used in conventional liquid state and solid state peptide syntheses. The latter syntheses involve first attaching an amino acid to a solid support and then building the peptide chain outward from this first, immobilized reactant. Materials and methods for use in the purification procedures which must be practiced to give usable intermediate and final products from such syntheses are also known. Hence, one might suppose that all that is needed to synthesize a peptide is, first of all, paper and pencil with which to draw the desired amino acid sequence, and then the known materials to subject to the known procedures.
In peptide synthesis, however, as in other fields of human endeavor, it is all too often the case that art does not imitate life. Despite all that is known, synthesizing significant amounts of peptides at a cost that permits their use in affordable pharmaceutical compositions is oftentimes extraordinarily difficult. And this has been found to be especially true in the case of Asp-Ser-Asp-Pro-Arg.